Use of ectone or ectone derivatives for oral care

ABSTRACT

The invention relates to the use of one or more compounds selected from compounds of formulae Ia and Ib, the physiologically compatible salts of compounds of formula Ia and Ib and the stereoisomer forms of compounds of formula La and Ib, wherein R 1 , R 2 , R 3 , R 4  and n have the meaning cited in claim  1.  Said compounds can be used advantageously in a preparation suitable for oral care.

[0001] The invention relates to preparations for oral care.

[0002] The oral cavity of humans is colonised by a large number ofcommensally living bacteria, the resident microflora, which are adaptedto the specific conditions in the oral chamber. The microflora of theoral cavity provides protection against colonisation by pathogenicmicroorganisms and is responsible for odour formation, i.e. the oralodour. The bacteria utilise the supply of nutrients in the oral cavityand on degradation of the nutrients form odorous substances, such as,for example, short-chain fatty acids. The microbial colonisation anddeposition of metabolic products on the teeth favours plaque formation.The microbial degradation products of carbohydrates from food result ina reduction in the pH and support caries formation. As a consequence ofacid formation by the plaque bacteria, microdecalcification of the teethoccurs. The bacteria should be protected by regular plaque removal andrestriction of frequent sugar intake and/or support for recalcificationby frequent fluoridation.

[0003] The object was therefore to provide preparations which aresuitable for oral care.

[0004] Surprisingly, it has now been found that this object is achievedby the use of one or more compounds selected from the compounds of theformulae Ia and Ib

[0005] the physiologically tolerated salts of the compounds of theformulae Ia and Ib, and the stereoisomeric forms of the compounds of theformulae Ia and Ib, where

[0006] R¹ is H or alkyl,

[0007] R² is H, COOH, COO-alkyl or CO—NH—R⁵,

[0008] R³ and R⁴ are each, independently of one another, H or OH,

[0009] n is 1, 2 or 3,

[0010] alkyl is an alkyl radical having from 1 to 4 carbon atoms, and

[0011] R⁵ is H, alkyl, an amino acid radical, dipeptide radical ortripeptide radical,

[0012] in preparations.

[0013] Ectoine protects the skin and mucous membrane microflora whichare important for an intact skin barrier against stress due todrying-out, free radicals, surfactants and high ion concentration. Theectoine/hydroxyectoine does not react with the cell metabolism.

[0014] Ectoines have the property of protecting cells, proteins,enzymes, DNA and biomembranes against removal of water molecules fromthe hydrate shell and stabilising the spatial structure of thebiopolymers.

[0015] The stabilisation of the resident oral flora by ectoine orderivatives thereof is an important prerequisite for the equilibrium ofthe micromedium of the oral mucous membrane and the formation of anintact oral cavity flora. Stabilisation of the resident oral flora meansthat transient, harmful bacteria find it more difficult to colonise.

[0016] Ectoine protects the oral mucous membrane against drying-out,surfactants and other chemicals. Colonisation of the oral mucousmembrane by pathogens, such as, for example, the pus-forming organismStaphylococcus aureus, is hindered or prevented by stabilisation of theresident flora. The moisturiser effect additionally makes colonisationby Staphylococcus aureus more difficult since these bacteria bind, inparticular, to collagen and fibronectin in damaged or dry skin.

[0017] The present invention relates to the use of one or more compoundsselected from the compounds of the formulae Ia and Ib

[0018] the physiologically tolerated salts of the compounds of theformulae Ia and Ib, and the stereoisomeric forms of the compounds of theformulae Ia and Ib, where

[0019] R¹ is H or alkyl,

[0020] R² is H, COOH, COO-alkyl or CO—NH—R⁵,

[0021] R³ and R⁴ are each, independently of one another, H or OH,

[0022] n is 1, 2 or 3,

[0023] alkyl is an alkyl radical having from 1 to 4 carbon atoms, and

[0024] R⁵ is H, alkyl, an amino acid radical, dipeptide radical ortripeptide radical,

[0025] in a preparation for oral care.

[0026] For the purposes of the present invention, the preparations fororal care include compositions for oral care and for dental care.

[0027] In a preferred embodiment, the present invention relates to theuse of one or more compounds selected from the above-mentioned compoundsof the formulae Ia and Ib, the physiologically tolerated salts of thecompounds of the formulae Ia and Ib, and the stereoisomeric forms of thecompounds of the formulae Ia and Ib in preparations for the protectionand care of the resident oral flora.

[0028] In a further preferred embodiment, the present invention relatesto the use of one or more compounds selected from the above-mentionedcompounds of the formulae Ia and Ib, the physiologically tolerated saltsof the compounds of the formulae Ia and Ib, and the stereoisomeric formsof the compounds of the formulae Ia and Ib in preparations for theprophylactic protection of teeth against damage to the dental enamel.

[0029] In a further preferred embodiment, the present invention relatesto the use of one or more compounds selected from the above-mentionedcompounds of the formulae Ia and Ib, the physiologically tolerated saltsof the compounds of the formulae Ia and Ib, and the stereoisomeric formsof the compounds of the formulae Ia and Ib in preparations for theprophylactic protection of the oral and pharyngeal mucous membrane.

[0030] The preparations comprising one or more compounds selected fromthe above-mentioned compounds of the formulae Ia and Ib, thephysiologically tolerated salts of the compounds of the formulae Ia andIb, and the stereoisomeric forms of the compounds of the formulae Ia andIb are used prophylactically.

[0031] For the purposes of the present invention, all compounds aboveand below selected from the above-mentioned compounds of the formulae Iaand Ib, the physiologically tolerated salts of the compounds of theformulae Ia and Ib, and the stereoisomeric forms of the compounds of theformulae Ia and Ib are referred to as “ectoine or ectoine derivatives”.

[0032] Ectoine and ectoine derivatives are low-molecular-weight, cyclicamino acid derivatives which can be isolated from various halophilicmicro-organisms. Both ectoine and hydroxyectoine have the advantage ofnot reacting with the cell metabolism.

[0033] The compounds selected from the above-mentioned compounds of theformulae Ia and Ib, the physiologically tolerated salts of the compoundsof the formulae Ia and Ib, and the stereoisomeric forms of the compoundsof the formulae Ia and Ib can be present in the preparations in the formof optical isomers, diastereomers, racemates, zwitterions, cations or amixture thereof. Of the compounds selected from the above-mentionedcompounds of the formulae Ia and Ib, the physiologically tolerated saltsof the compounds of the formulae Ia and Ib, and the stereoisomeric formsof the compounds of the formulae Ia and Ib, preference is given to thosecompounds in which R¹ is H or CH₃, R² is H or COOH, R³ and R⁴ are each,independently of one another, H or OH, and n is 2. Of the compoundsselected from the above-mentioned compounds of the formulae Ia and Ib,the physiologically tolerated salts of the compounds of the formulae Iaand Ib, and the stereoisomeric forms of the compounds of the formulae Iaand Ib, particular preference is given to the compounds(S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid (ectoine)and (S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylicacid (hydroxyectoine).

[0034] The term “amino acid” is taken to mean the stereoisomeric forms,for example D and L forms, of the following compounds: alanine,β-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine,glutamic acid, glycine, histidine, isoleucine, leucine, lysine,methionine, phenylalanine, serine, threonine, tryptophan, tyrosine,valine, γ-aminobutyrate, Nε-acetyllysine, Nδ-acetylornithine,Nγ-acetyldiaminobutyrate and Nα-acetyldiaminobutyrate. L-amino acids arepreferred.

[0035] Amino acid radicals are derived from the corresponding aminoacids.

[0036] The radicals of the following amino acids are preferred: alanine,β-alanine, asparagine, aspartic acid, glutamine, glutamic acid, glycine,serine, threonine, valine, γ-aminobutyrate, Nε-acetyllysine,Nδ-acetylornithine, Nγ-acetyldiaminobutyrate andNα-acetyldiaminobutyrate.

[0037] The di- and tripeptide radicals are acid amides from the point ofview of their chemical nature and decompose on hydrolysis to give 2 or 3amino acids. The amino acids in the di- and tripeptide radicals arebonded to one another by amide bonds. Preferred di- and tripeptideradicals are built up from the preferred amino acids.

[0038] The alkyl groups include the methyl group CH₃, the ethyl groupC₂H₅, the propyl groups CH₂CH₂CH₃ and CH(CH₃)₂ and the butyl groupsCH₂CH₂CH₂CH₃, H₃CCHCH₂CH₃, CH₂CH(CH₃)₂ and C(CH₃)₃. The preferred alkylgroup is the methyl group.

[0039] Preferred physiologically tolerated salts of the compounds of theformulae Ia and Ib are, for example, alkali metal, alkaline earth metalor ammonium salts, such as Na, K, Mg or Ca salts, and salts derived fromthe organic bases triethylamine or tris(2-hydroxyethyl)amine. Furtherpreferred physiologically tolerated salts of the compounds of theformulae Ia and Ib are formed by reaction with inorganic acids, such ashydrochloric acid, sulfuric acid and phosphoric acid, or with organiccarboxylic or sulfonic acids, such as acetic acid, citric acid, benzoicacid, maleic acid, fumaric acid, tartaric acid and p-toluenesulfonicacid.

[0040] Compounds of the formulae Ia and Ib in which basic and acidicgroups, such as carboxyl or amino groups, are present in the same numberform internal salts.

[0041] The preparation of the compounds of the formulae Ia and Ibisdescribed in the literature (DE 43 42 550).(S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid and(S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylic acidcan also be obtained microbiologically (Severin et al., J. Gen.Microb.138 (1992) 1629-1638).

[0042] In a preferred embodiment, the preparation comprises one or moreanti-oxidants. The preparations can comprise the antioxidants known fromthe specialist literature, for example flavonoids, coumaranones, aminoacids (for example glycine, histidine, tyrosine, tryptophan) andderivatives thereof, imidazoles (for example urocanic acid) andderivatives thereof, peptides, such as D,L-carnosine, D-carnosine,L-carnosine and derivatives thereof (for example anserine), carotenoids,carotines (for example α-carotine, β-carotine, lycopine) and derivativesthereof, chlorogenic acid and derivatives thereof, lipoic acid andderivatives thereof (for example dihydrolipoic acid), aurothioglucose,propylthiouracil and other thiols (for example thioredoxin, glutathione,cysteine, cystine, cystamine and glycosyl, N-acetyl, methyl, ethyl,propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl,cholesteryl and glyceryl esters thereof) and salts thereof,diaurylthiodipropionate, distearylthiodipropionate, thiodipropionic acidand derivatives thereof (esters, ethers, peptides, lipids, nucleotides,nucleosides and salts) and sulfoximine compounds (for example buthioninesulfoximines, homocysteine sulfoximine, buthionine sulfones, penta-,hexa-, heptathionine sulfoximine), in very small tolerated doses (forexample from pmol to μmol/kg), furthermore (metal) chelating agents (forexample α-hydroxyfatty acids, palmitic acid, phytic acid, lactoferrin),α-hydroxy acids (for example citric acid, lactic acid, malic acid),humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTAand derivatives thereof, unsaturated fatty acids and derivativesthereof, vitamin C and derivatives thereof (for example ascorbylpalmitate, magnesium ascorbyl phosphate, ascorbyl acetate) and coniferylbenzoate of benzoic resin, rutic acid and derivatives thereof,α-glycosylrutin, ferulic acid, furfurylideneglucitol, carnosine,butylhydroxytoluene (BHT), butylhydroxyanisole, nordohydroguaiareticacid, trihydroxybutyrophenone, uric acid and derivatives thereof,mannose and derivatives thereof, zinc and derivatives thereof (forexample ZnO, ZnSO₄), selenium and derivatives thereof (for exampleselenium methionine), stilbenes and derivatives thereof (for examplestilbene oxide, trans-stilbene oxide).

[0043] Mixtures of antioxidants are likewise suitable for use in thepreparations. Known and commercial mixtures are, for example, mixturescomprising, as active ingredients, lecithin, L-(+)-ascorbyl palmitateand citric acid (for example Oxynex® AP), natural tocopherols,L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid and citric acid (forexample Oxynex® K LIQUID), tocopherol extracts from natural sources,L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid and citric acid (forexample Oxynex® L LIQUID), DL-α-tocopherol, L-(+)-ascorbyl palmitate,citric acid and lecithin (for example Oxynex® LM) or butylhydroxytoluene(BHT), L-(+)-ascorbyl palmitate and citric acid (for example Oxynex®2004).

[0044] In a particularly preferred embodiment of the invention, thepreparation comprises one or more compounds selected from flavonoidsand/or coumaranones.

[0045] In a further particularly preferred embodiment of the invention,the preparation comprises, as antioxidant, one of the above-mentionedmixtures comprising lecithin, L-(+)-ascorbyl palmitate and citric acid(for example Oxynex® AP), natural tocopherols, L-(+)-ascorbyl palmitate,L-(+)-ascorbic acid and citric acid (for example Oxynex® K LIQUID),tocopherol extracts from natural sources, L-(+)-ascorbyl palmitate,L-(+)-ascorbic acid and citric acid (for example Oxynex® L LIQUID),DL-α-tocopherol, L-(+)-ascorbyl palmitate, citric acid and lecithin (forexample Oxynex® LM) or butylhydroxytoluene (BHT), L-(+)-ascorbylpalmitate and citric acid (for example Oxynex® 2004). Particularpreference is furthermore given to embodiments comprising one of thesemixtures and flavonoids.

[0046] The term flavonoids covers the glycosides of the flavanones,flavones, 3-hydroxyflavones (=flavonols), aurones, isoflavones androtenoids [Römpp Chemie Lexikon [Römpp's Lexicon of Chemistry], Volume9, 1993]. For the purposes of the present invention, however, it is alsotaken to mean the aglycones, i.e. the sugar-free constituents, and thederivatives of the flavonoids and the aglycones. For the purposes of thepresent invention, the term coumaranones is also taken to mean thederivatives thereof.

[0047] Preferred flavonoids are derived from flavanones, flavones,3-hydroxyflavones, aurones and isoflavones, in particular fromflavanones, flavones, 3-hydroxyflavones and aurones.

[0048] The flavanones are characterised by the following basicstructure:

[0049] The flavones are characterised by the following basic structure:

[0050] The 3-hydroxyflavones (flavonols) are characterised by thefollowing basic structure:

[0051] The isoflavones are characterised by the following basicstructure:

[0052] The aurones are characterised by the following basic structure:

[0053] The coumaranones are characterised by the following basicstructure:

[0054] The flavonoids and coumaranones are preferably selected from thecompounds of the formula (I):

[0055] in which

[0056] Z₁ to Z₄ are each, independently of one another, H, OH, alkoxy,hydroxyalkoxy, mono- or oligoglycoside radicals, where the alkoxy andhydroxyalkoxy groups may be branched or unbranched and can have from 1to 18 carbon atoms, and where sulfate or phosphate may also be bonded tothe hydroxy groups of the said radicals,

[0057] A is selected from the group consisting of the sub-formulae (IA),(IB) and (IC)

[0058] Z₅ is H, OH or OR,

[0059] R is a mono- or oligoglycoside radical,

[0060] Z₆ to Z₁₀ are as defined for the radicals Z₁ to Z₄, and

[0061] The alkoxy groups are preferably linear and have from 1 to 12 andpreferably from 1 to 8 carbon atoms. These groups thus conform to theformula —O—(CH₂)_(m)—H, where m is 1, 2, 3, 4, 5, 6, 7 or 8 and inparticular is from 1 to 5.

[0062] The hydroxyalkoxy groups are preferably linear and have from 2 to12 and preferably from 2 to 8 carbon atoms. These groups thus conform tothe formula —O—(CH₂)_(n)—OH, where n is 2, 3, 4, 5, 6, 7 or 8, inparticular from 2 to 5 and extremely preferably 2.

[0063] The mono- and oligoglycoside radicals are preferably built upfrom 1 to 3 glycoside units. These units are preferably selected fromthe group consisting of the hexosyl radicals, in particular therhamnosyl radicals and glucosyl radicals. However, other hexosylradicals, for example allosyl, altrosyl, galactosyl, gulosyl, idosyl,mannosyl and talosyl, can, if desired, advantageously be used. It mayalso be advantageous in accordance with the invention to use pentosylradicals.

[0064] In a preferred embodiment,

[0065] Z₁ and Z₃ are H,

[0066] Z₂ and Z₄ are other than H, in particular OH, methoxy, ethoxy or2-hydroxyethoxy,

[0067] Z₅ is H, OH or OR, where R is a glycoside radical which is builtup from 1 to 3, preferably 1 or 2, glycoside units,

[0068] Z₆, Z₉ and Z₁₀ are H, and

[0069] Z₇ and Z₈ are other than H, in particular OH, methoxy, ethoxy or2-hydroxyethoxy.

[0070] In a further particularly preferred embodiment of the invention,in particular if the water solubility of the flavonoids and coumaranonesis to be increased, a sulfate or phosphate group is bonded to thehydroxyl groups. Suitable counterions are, for example, the ions of thealkali or alkaline earth metals, these being selected, for example, fromsodium and potassium.

[0071] The flavonoids are preferably selected from the followingcompounds: 4,6,3′,4′-tetrahydroxyaurone, quercetin, rutin, isoquercetin,eriodictyol, taxifolin, luteolin, trishydroxyethylquercetin(troxequercetin), trishydroxyethylrutin (troxerutin),trishydroxyethylisoquercetin (troxeisoquercetin),trishydroxyethylluteolin (troxeluteolin) and sulfates and phosphatesthereof.

[0072] Of the flavonoids, particular preference is given to rutin andtroxerutin. Very particular preference is given to troxerutin.

[0073] Of the coumaranones, preference is given to4,6,3′,4′-tetrahydroxybenzyl-3-coumaranone.

[0074] The proportion of the one or more antioxidants in the preparationis preferably from 0.001 to 5% by weight, particularly preferably from0.01 to 2% by weight, based on the preparation as a whole.

[0075] Furthermore, the preparations may also comprise, for example,anthocyanidine (cyanidine).

[0076] The preparations are prepared by converting one or more compoundsselected from the above-mentioned compounds of the formulae Ia and Ib,the physiologically tolerated salts of the compounds of the formulae Iaand Ib, and the stereoisomeric forms of the compounds of the formulae Iaand Ib into a suitable preparation form, if desired with adjuvantsand/or excipients. The adjuvants and excipients originate from the groupconsisting of the vehicles, preservatives and other conventionalassistants.

[0077] The preparations based on one or more compounds selected from theabove-mentioned compounds of the formulae Ia and Ib, the physiologicallytolerated salts of the compounds of the formulae Ia and Ib, and thestereoisomeric forms of the compounds of the formulae Ia and Ib are usedin the adminstration forms which are conventional in oral and pharyngealhygiene.

[0078] Suitable use forms are all administration forms used for oralhygiene, for example solutions, emulsions, suspensions, such as, forexample, pastes, gels, surfactant-containing cleaning preparations andsprays, such as, for example, aerosol sprays and pump sprays. Inaddition to the one or more compounds selected from the above-mentionedcompounds of the formulae Ia and Ib, the physiologically tolerated saltsof the compounds of the formulae Ia and Ib, and the stereoisomeric formsof the compounds of the formulae Ia and Ib, any desired conventionalexcipients, adjuvants and, if desired, further active ingredients can beadded to the preparation.

[0079] Preferred adjuvants originate from the group consisting of thepreservatives, antioxidants, stabilisers, solubilisers, vitamins,colorants, odour improvers, thickening agents, humectants, abrasives andscouring media, foaming agents, thickeners, binders and flavours.

[0080] Besides one or more compounds selected from the above-mentionedcompounds of the formulae Ia and Ib, the physiologically tolerated saltsof the compounds of the formulae Ia and Ib, and the stereoisomeric formsof the compounds of the formulae Ia and Ib, solutions and emulsions cancomprise the conventional excipients, such as solvents, solubilisers andemulsifiers, for example water, ethanol, isopropanol, ethyl carbonate,ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol,1,3-butyl glycol, oils, in particular essential oils, such as peppermintoil, clove oil, aniseed oil, fennel oil, sage oil, glycerol fatty acidesters, hydrogenated castor oils, polyethylene glycols and fatty acidesters of sorbitan, polysorbates or mixtures of these substances.

[0081] The emulsions can exist in various forms. For example, they canbe, for example, an emulsion or microemulsion of the water-in-oil (W/O)type or of the oil-in-water (O/W) type, or a multiple emulsion, forexample of the water-in-oil-in-water (W/O/W) type.

[0082] The preparations may also be in the form of emulsifier-free,disperse preparations. They can be, for example, hydrodispersions orPickering emulsions.

[0083] Besides one or more compounds selected from the above-mentionedcompounds of the formulae Ia and Ib, the physiologically tolerated saltsof the compounds of the formulae Ia and Ib, and the stereoisomeric formsof the compounds of the formulae Ia and Ib, suspensions can comprise theconventional excipients, such as liquid diluents and humectants, forexample water, ethanol or propylene glycol, sorbitol, glycerol,suspension media, for example ethoxylated isostearyl alcohols,polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters,microcrystalline cellulose, aluminium metahydroxide, bentonite,agar-agar and tragacanth, or mixtures of these substances.

[0084] Besides one or more compounds selected from the above-mentionedcompounds of the formulae Ia and Ib, the physiologically tolerated saltsof the compounds of the formulae Ia and Ib, and the stereoisomeric formsof the compounds of the formulae Ia and Ib, gels can comprise theconventional excipients, for example animal and vegetable fats, waxes,paraffins, starch, tragacanth, cellulose derivatives, polyethyleneglycols, silicones, bentonites, silica, talc and zinc oxide, or mixturesof these substances.

[0085] Besides one or more compounds selected from the above-mentionedcompounds of the formulae Ia and Ib, the physiologically tolerated saltsof the compounds of the formulae Ia and Ib, and the stereoisomeric formsof the compounds of the formulae Ia and Ib, surfactant-containingcleaning products can comprise the conventional excipients, such assalts of fatty alcohol sulfates, fatty alcohol ether sulfates,sulfosuccinic acid monoesters, fatty acid albumen hydrolysates,isothionates, imidazolinium derivatives, methyl taurates, sarcosinates,fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols,fatty acid glycerides, fatty acid diethanolamides, vegetable andsynthetic oils, lanolin derivatives, ethoxylated glycerol fatty acidesters, or mixtures of these substances.

[0086] Besides one or more compounds selected from the above-mentionedcompounds of the formulae Ia and Ib, the physiologically tolerated saltsof the compounds of the formulae Ia and Ib, and the stereoisomeric formsof the compounds of the formulae Ia and Ib, sprays can comprise theconventional excipients, for example lactose, talc, silica, aluminiumhydroxide, calcium silicate and polyamide powders, or mixtures of thesesubstances. They may additionally comprise the conventional propellants,for example chlorofluorocarbons, propane/butane or dimethyl ether.

[0087] The oral and dental care compositions can be, for example, in theform of toothpastes, liquid tooth creams, tooth powders, mouthwashes or,if desired, also in the form of a chewing composition, for example inthe form of chewing gum. However, they are preferably in the form ofmore or less flowable or plastic toothpastes, as are used for cleaningteeth using a toothbrush.

[0088] The toothpastes or liquid tooth creams comprise a polishingagent, usually in an amount of from 5 to 50% by weight, and a humectant,usually in an amount of 10-60% by weight.

[0089] Suitable polishing agents are all abrasive media which are knownfor toothpastes, such as, for example, silicas, aluminium hydroxide,aluminium oxide, calcium pyrophosphate, chalk, dicalcium phosphatedihydrate (CaHPO₄.2H₂O), sodium aluminium silicates, such as, forexample, zeolite A, organic polymers, such as, for example,polymethacrylate, or mixtures of these abrasive media.

[0090] Suitable vehicles for the toothpastes, which enable a suitableconsistency to be established for dispensing from tubes, dispensingcontainers or flexible bottles, are, for example, a combination ofhumectants, binders and water.

[0091] Humectants which can be employed are, for example, glycerol,sorbitol, xylitol, propylene glycols, polyethylene glycols, inparticular those having mean molecular weights of 200-800. Theconsistency regulators (or binders) used are, for example, naturaland/or synthetic water-soluble polymers, such as alginates,carragheenates, tragacanth, starch and starch ethers, cellulose ethers,such as, for example, carboxymethylcellulose (Na salt),hydroxyethylcellulose, methylhydroxypropylcellulose, guar, acacia gum,agar-agar, xanthan gum, succinoglycan gum, carob-seed flour, pectins,water-soluble carboxyvinyl polymers (for example Carbopol® grades),polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycols, inparticular those having molecular weights of 1500-1,000,000.

[0092] Further substances which are suitable for viscosity control are,for example, phyllosilicates, such as, for example, montmorilloniteclays, colloidal thickening silicas, such as, for example, aerogelsilicas, pyrogenic silicas or microground precipitation silicas. It isalso possible to use viscosity-stabilising additives from the groupconsisting of cationic, zwitterionic or ampholytic nitrogen-containingsurfactants, hydroxypropyl-substituted hydrocolloids or polyethyleneglycol-polypropylene glycol copolymers having a mean molecular weight offrom 1000 to 5000, or a combination of the said compounds, in thetoothpastes.

[0093] In order to support the cleaning action and if desired also forthe development of foam during tooth brushing and for stabilisation ofthe polishing media dispersion in the vehicle, the toothpastes alsocomprise surface-active substances in an amount of 0.1-5% by weight.

[0094] Suitable surfactants are, for example, linear sodiumalkylsulfates having 12-18 carbon atoms in the alkyl group. Thesesubstances additionally have an enzyme-inhibiting action on thebacterial metabolism of plaque. Further suitable surfactants are alkalimetal salts, preferably sodium salts, of alkylpolyglycol ether sulfatehaving 12-16 carbon atoms in the linear alkyl group and 2-6 glycol ethergroups in the molecule, of linear alkane(C₁₂-C₁₈)sulfonate, ofsulfosuccinic acid monoalkyl(C₁₂-C₁₈) esters, of sulfated fatty acidmonoglycerides, sulfated fatty acid alkanolamides, sulfoacetic acidalkyl(C₁₂-C₁₆) esters, alkylsarcosines, acyltaurides andacylisothionates, each having 8-18 carbon atoms in the acyl group. Alsosuitable are zwitterionic, ampholytic and nonionic surfactants, forexample oxyethylates of fatty acid mono- and diglycerides, of fatty acidsorbitan esters and alkyl(oligo)glucosides.

[0095] Further conventional additives to the oral and dental carecompositions, in particular to toothpastes, are

[0096] sweeteners, such as, for example, saccharin-sodium, sodiumcyclamate, sucrose, lactose, maltose and fructose,

[0097] flavours, such as, for example, peppermint oil, spearmint oil,eucalyptus oil, aniseed oil, fennel oil, caraway seed oil, menthylacetate, cinnamaldehyde, anethole, vanillin, thymol, and mixtures ofthese and other natural and synthetic flavours,

[0098] pigments, such as, for example, titanium dioxide,

[0099] dyes,

[0100] buffer substances, such as, for example, primary, secondary ortertiary alkali metal phosphates or citric acid/sodium citrate.

[0101] The oral and dental care compositions, in particular thetoothpastes, may comprise other active ingredients in addition toectoine.

[0102] The oral and dental care compositions, in particular thetoothpastes, may comprise, for example, anticaries active ingredients.These can be selected, for example, from organic and inorganicfluorides, for example from sodium fluoride, potassium fluoride, sodiummonofluorophosphate, tin fluoride and sodium fluorosilicate.

[0103] The oral and dental care compositions, in particular thetoothpastes, may also comprise, for example, substances which areeffective against tartar. Substances of this type can be, for example,chelating agents, such as, for example, ethylenediaminetetraacetic acidand sodium salts thereof, pyrophosphate salts, such as the water-solubledialkali metal or tetraalkali metal pyrophosphate salts, for exampleNa₄P₂O₇, K₄P₂O₇, Na₂K₂P₂O₇, Na₂H₂P₂O₇ and K₂H₂P₂O₇, or polyphosphatesalts, which can be selected, for example, from water-soluble alkalimetal tripolyphosphates, such as sodium tripolyphosphate and potassiumtripolyphosphate.

[0104] The oral and dental care compositions, in particular thetoothpastes, may also comprise, for example, antimicrobial substances aspreservatives or as antiplaque active ingredients. Substances of thistype can be selected, for example, from methyl, ethyl or propylp-hydroxybenzoate, sodium sorbate, sodium benzoate, bromochlorophen,triclosane, phenylsalicylic acid esters, biguanides, for examplechlorhexidine, thymol, etc.

[0105] The oral and dental care compositions, in particular thetoothpastes, may also comprise, for example, wound-healing andinflammation-inhibiting substances, for example active ingredientsagainst gum inflammation. Substances of this type may be selected, forexample, from allantoin, azulene, camomile extracts, tocopherol,panthenol, bisabolol and sage extracts.

[0106] The oral and dental care compositions, in particular thetoothpastes, may also comprise substances for increasing themineralisation potential, for example calcium-containing substances,such as, for example, calcium chloride, calcium acetate and dicalciumphosphate dihydrate. The concentration of the calcium-containingsubstance depends on the solubility of the substance and on theinteraction with other substances present in the oral and dental carecomposition.

[0107] The oral and dental care compositions, in particular thetoothpastes, may also comprise substances which increase theinsensitivity of the teeth, for example potassium salts, such as, forexample, potassium nitrate, potassium citrate, potassium chloride,potassium bicarbonate and potassium oxalate.

[0108] In mouthwashes, the vehicle essentially consists of water,ethanol, essential oils, emulsifiers and solubilisers for the ectoineand the flavour components, flavour correctants (for example sweeteners)and, if desired, astringent or invigorating drug extracts and, ifdesired, dyes. Further active ingredients which may be present are, forexample, antimicrobial substances, such as chlorhexidine or triclosane.

[0109] In a further preferred embodiment, the preparation comprises oneor more enzymes. The enzyme(s) is (are) preferably selected from thegroup consisting of glucose oxidase, amyloglucosidase andlactoperoxidase. The enzymes may have, for example, an antiplaqueactivity. For example, the addition of the enzyme glucose oxidase duringoxidative glucose degradation may result in the liberation of hydrogenperoxide, thus combating plaque.

[0110] However, enzymes frequently have low stability and are exposed invitro to a number of destabilising conditions. For example, substancesof this type are sensitive to changes in the medium surrounding them andto temperature variations. The storage of enzymes over an extendedperiod therefore results in a decrease in activity. The use of enzymesin preparations for oral care is particularly difficult since theseproducts are subjected to large temperature and humidity variations.Destabilisation of the enzymes can thus occur before they reach the siteof action from the preparation.

[0111] The problem of the decrease in the activity of enzymes alsoarises, in particular, in preparations in which they have to have thehighest possible activity over an extended period. This is the case, forexample, in preparations with uniform liberation of the enzymes over anextended period, which is also known as the “depot effect”.

[0112] For the above-mentioned reasons, it is necessary to stabiliseenzymes in preparations. It has been found that the stabilisation ofenzymes present in preparations for oral care is achieved by thecompounds selected from the above-mentioned compounds of the formulae Iaand Ib, the physiologically tolerated salts of the compounds of theformulae Ia and Ib, and the stereoisomeric forms of the compounds of theformulae Ia and Ib which are like-wise present in the preparation.

[0113] The proportion of the compounds selected from the above-mentionedcompounds of the formulae Ia and Ib, the physiologically tolerated saltsof the compounds of the formulae Ia and Ib, and the stereoisomeric formsof the compounds of the formulae Ia and Ib in the preparation ispreferably from 0.001 to 50% by weight, particularly preferably from0.01 to 10% by weight and especially preferably from 0.1 to 10% byweight, based on the preparation as a whole.

[0114] All compounds or components which can be used in the preparationsare either known and commercially available or can be synthesised byknown methods.

[0115] The following examples serve to illustrate the invention and arein no way to be regarded as a limitation. All % data are per cent byweight.

[0116] The INCI names of raw materials used are as follows: Raw materialINCI name Karion F liquid Sorbitol, Aqua Peppermint aroma AromaPhoskadent NA 211 Sodium Monofluorophosphate Polyethylene glycol 400 DABPEG-8 RonaCare ™ CPC N-Cetylpyridinium Chloride Monohydrate RonaCareEctoine Ectoine RonaCare NaF Sodium Fluoride RonaCare ™ OlaflurBis(hydroxyethyl)aminopropyl- N-hydroxy- ethyl-octadecylaminedihydrofluoride, 33% in 1,2-propanediol Sident 12 Silica Sipernat 22 SHydrated Silica Tego Betaine BL 215 Cocamidopropyl Betaine Tego BetaineF 50 Cocamidopropyl Betaine Tego Betaine ZF Cocamidopropyl BetaineTrihydroxyethylrutin Troxerutin

EXAMPLE 1

[0117] A mouthwash concentrate comprising ectoine is prepared from thefollowing components: % by wt. RonaCare ™ CPC (Art. No. 102340) (1) 0.2RonaCare ™ Olaflur (Art. No. 11680) (1) 0.5 RonaCare ™ Ectoine (Art. No.130200) (1) 1.0 Ethanol (96%) (Art. No. 100971) (1) 20.0 Menthol (Art.No. 105995) (1) 0.2 Tego-Betaine BL 215 (2) 5.0 Glycerol (87%) (Art. No.104091) (1) 12.0 Water, demineralised to 100

[0118] Preparation:

[0119] Phase A is stirred until a clear solution is formed.

[0120] Sources of Supply:

[0121] (1) Merck KGaA

[0122] (2) Goldschmidt AG

EXAMPLE 2

[0123] A tooth gel comprising ectoine is prepared from the followingcomponents: % by wt. A RonaCare NaF (Art. No. 106441) (1) 0.1 RonaCareEctoine (Art. No. 130200) (1) 1.0 Sodium benzoate (Art. No. 106290) (1)0.2 Sodium saccharin (Art. No. 817042) (1) 0.2 Phoskadent (2) 0.75Karion F liquid (Art. No. 102993) (1) 65.0 Water, demineralised to 100 BBromochlorophene (Art. No. 103281) (1) 0.1 Peppermint aroma 77526-34 (3)1.0 Polyethylene glycol 400 DAB (3) 3.0 C Sident 12 (4) 8.5 Sipernat 22S (4) 7.5 D Pearlescent pigments (1) 0.05 Tego-Betaine F 50 (5) 5.0

[0124] Preparation:

[0125] Phases A and B are pre-mixed separately from one another andcombined. Phase C is then slowly added with stirring, and the mixture issubsequently warmed to 50° C. under reduced pressure. Phase D is addedto the clear gel, the mixture is stirred slowly under reduced pressureuntil free from air, and then allowed to cool to room temperature.

[0126] Sources of Supply:

[0127] (1) Merck KGaA

[0128] (2) Benckiser-Knapsack GmbH

[0129] (3) Givaudan-Roure GmbH

[0130] (4) Degussa AG

[0131] (5) Th. Goldschmidt AG

EXAMPLE 3

[0132] A tooth gel comprising ectoine is prepared from the followingcomponents: % by wt. A RonaCare ™ NaF (1) 0.08 RonaCare ™ Ectoine (1)1.00 Trihydroxyethylrutin (1) 0.50 Karion F liquid (1) 62.13 Sodiumbenzoate (1) 0.20 Sodium saccharinate 0.20 Water, demineralised 9.00 BRonaCare ™ Olaflur (1) 1.50 Bromochlorophene (1) 0.10 Aroma 35049 (2)1.00 C Polyethylene glycol 400 (1) 3.00 Tego Betaine ZF (3) 5.00 SicometPatent Blue (E131), 0.1% in (4) 0.80 Water to 100 D Sident 12 (5) 9.50Sipernat 22 S (5) 7.50

[0133] Preparation:

[0134] Phases A and B are pre-mixed separately from one another. Phase Cis heated to 50° C., phases A and B are stirred into phase C, and thephases are subsequently mixed under reduced pressure. After slowaddition of phase D, the mixture is homogenised under reduced pressure.Stirring is continued under reduced pressure until the gel is clear.

[0135] Sources of Supply:

[0136] (1) Merck KGaA

[0137] (2) Orissa Drebing GmbH

[0138] (3) Th. Goldschmidt AG

[0139] (4) BASF AG

[0140] (5) Degussa AG.

1. Use of one or more compounds selected from the compounds of theformulae Ia and Ib

the physiologically tolerated salts of the compounds of the formulae Iaand Ib, and the stereoisomeric forms of the compounds of the formulae Iaand Ib, where R¹ is H or alkyl, R is H, COOH, COO-alkyl or CO—NH—R⁵, R³and R⁴ are each, independently of one another, H or OH, n is 1, 2 or 3,alkyl is an alkyl radical having from 1 to 4 carbon atoms, and R⁵ is H,alkyl, an amino acid radical, dipeptide radical or tripeptide radical,in a preparation for oral care.
 2. Use according to claim 1 for theprotection and care of the resident oral flora.
 3. Use according to oneof claims 1 and 2 for the prophylactic protection of teeth againstdamage to the dental enamel.
 4. Use according to one or more of claims 1to 3 for the prophylactic protection of the oral and pharyngeal mucousmembrane.
 5. Use according to one or more of claims 1 to 4,characterised in that use is made of one or more compounds selected fromthe above-mentioned compounds of the formulae Ia and Ib, thephysiologically tolerated salts of the compounds of the formulae Ia andIb, and the stereoisomeric forms of the compounds of the formulae Ia andIb for use in the form of a solution, an emulsion, a suspension, apaste, a gel, a surfactant-containing cleaning preparation, a spray, acream, a powder, a mouthwash or a chewing composition.
 6. Use accordingto one or more of claims 1 to 5, characterised in that the proportion ofthe compounds selected from the above-mentioned compounds of theformulae Ia and Ib, the physiologically tolerated salts of the compoundsof the formulae Ia and Ib, and the stereoisomeric forms of the compoundsof the formulae Ia and Ib is from 0.001 to 50% by weight, based on thepreparation as a whole.
 7. Use according to one or more of claims 1 to6, characterised in that the compounds of the formulae Ia and Ib areselected from the compounds(S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid and(S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylic acid.8. Use according to one or more of claims 1 to 7, characterised in thatthe preparation comprises one or more antioxidants.
 9. Use according toone or more of claims 1 to 8, characterised in that the preparationcomprises one or more enzymes.